Functional dyspepsia (FD) affects ~15% of the population. While numerous findings have been associated with these patients including reduced volume of tolerance to nutritive drinks, the pathophysiology and treatment of this condition remain unclear. Postprandial bloating is a key symptom of FD with patients noting abdominal distension after meals. Bloating is a symptom shared with irritable bowel syndrome (IBS), another functional bowel disorder with a prevalence of ~15%. Recently, we have shown that up to 84% of patients with IBS have an abnormal pattern of bacterial gas excretion on lactulose breath test (LBT) to suggest small intestinal bacterial overgrowth (SIBO). SIBO is the abnormal expansion of the indigenous gut bacterial flora proximally into the small intestine. SIBO is associated with leaky gut, bacterial translocation and immune activation to represent a shift in host-gut bacterial relationship. In this setting, bacterial fermentation takes place in both the small and large intestine resulting in excessive production of bacterial gases leading to bloating and distension. In a randomized, placebo- controlled antibiotic treatment of IBS, successful treatment of SIBO results in a significant improvement of both gastrointestinal symptoms such as bloating and extraintestinal symptoms such as fatigue. Objective: We will determine the prevalence and association of SIBO, abnormal interdigestive motility, and hypersensitivity in FD. We will also determine the relationship between SIBO and hypersensitivity of FD using randomized antibiotic treatment. Research design: We will compare in a cohort of FD patients and healthy controls breath testing, interdigestive motility and hypersensitivity. A nonabsorbable, small-bowel targeting antibiotic treatment will be administered in a randomized, double, blind, placebo-controlled manner. Methodology: We will recruit patients with negative upper gastrointestinal endoscopy and negative 24h pH study who meet the inclusion criteria for FD along with healthy controls. We will compare symptom scores recorded on questionnaires, LBT results, small bowel manometry, and volume of tolerance of a nutritive drink before and after treatment of SIBO. Clinical relationships: FD has been a perplexing and disabling disorder affecting ~15% of population. Current treatment is directed at symptom reduction but is characterized by poor efficacy. The identification of a gut bacterial explanation for FD will lead to the development of novel diagnostic and treatment approaches targeting SIBO. This will represent a major advance in the clinical care of FD patients. Public Health Relevance Functional dyspepsia with a prevalence of up to ~15% of the population is a common but poorly understood disorder without effective treatment. Bloating is a key complaint of these patients. In this proposal, we will test the hypothesis that excessive bacterial fermentation may play a role in the bloating and other dyspeptic symptoms of functional dyspepsia. [unreadable] [unreadable] [unreadable]